Electrospinning uses an electrical charge to draw fine (typically on the micro or nano scale) fibres from a liquid. It is a robust technique for fabricating polymer fibrous meshes mimicking the extracellular matrices (ECM) of natural tissues. (Pham, et al. 2006 Tissue Engineering 12, (5), 1197-1211.) Electrospinning shares characteristics of both electrospraying and conventional solution dry spinning of fibers. By adjusting the viscosity and surface tension of the polymer solution as well as the voltage, speed and duration of the electrospinning process, polymer fibrous meshes of varied fiber dimensions and mesh thicknesses and porosities could be obtained. (Huang, et al. 2003 Composites Science and Technology 63 (15), 2223-2253; Li, et al. 2004 Advanced Materials 16 (14), 1151-1170.) For in vivo tissue engineering applications, however, these fibrous meshes should also be engineered with proper biochemical microenvironment (e.g., via the retention of tissue-specific biological cues) to help support cellular attachment, direct stem cell differentiation, and guide tissue integration.
Covalent modification of synthetic scaffolds with growth factors was previously attempted for expediting bone tissue repair. (Uludag, et al. 2000 Biotechnol. Prog. 16 (2), 258-267; Gittens, et al. 2004 Journal of Controlled Release 98 (2), 255-268.) This approach, however, risks compromising the bioactivity of the proteins due to substantial structural perturbation. (Katagiri, et al. 1994 Journal of Cell Biology 127 (6), 1755-1766; Uludag, et al. 1999 Biotechnol. Bioeng. 65 (6), 668-672.) By contrast, strategies for retaining protein therapeutics through non-covalent electrostatic interactions are more biomimetic in nature. For instance, sulfated polysaccharides are known for their high affinity for many endogenous proteins within the ECM environment such as various isoforms of bone morphogenetic proteins (BMPs), presumably through favorable electrostatic interactions between the sulfate residues and the basic amino acid residues of the proteins. (Vukicevic, et al. 1994 Biochem. Biophys. Res. Commun. 198 (2), 693-700; Irie, et al. 2003 Biochem. Biophys. Res. Commun. 308 (4), 858-865; Ruppert, et al. 1996 Eur. J. Biochem. 237, (1), 295-302; Takada, et al. 2003 Journal of Biological Chemistry 278, (44), 43229-43235.) Such biopolymers are ideal candidates for the fabrication of synthetic tissue scaffolds. Indeed, chondroitin sulfate, an important sulfated structural component of cartilage tissue, has been shown to enhance bone remodeling of musculoskeletal defects when used in combination with other bone grafting materials. (Schneiders, et al. 2008 Journal of Orthopaedic Research, DOI 10.1002/jor.20719.) The application of electrospun chondroitin sulfate fibrous meshes to augment the performance of 3-dimensional tissue engineered constructs, however, has proven challenging due to their exceptionally high solubility in water. In our hands, for example, methacrylating chondroitin sulfate with glycidyl methacrylate (Li, et al. 2004 Journal of Biomedical Materials Research Part A 68A (1), 28-33.) prior to electrospinning, followed by covalent crosslinking of the electrospun meshes, failed to improve the stability of the mesh in water.
Thus, an urgent unmet need remains for combining suitable polymers with practical fabrication methods to prepare biocompatible synthetic tissue scaffolds.